MARCH5对卵巢癌细胞糖代谢的调控作用研究

Effect of MARCH5 on glucose metabolism in ovarian cancer cells

目的探讨膜相关锌指蛋白5(MARCH5)在卵巢癌细胞糖代谢中的调控作用。方法将卵巢癌SKOV3细胞分为对照组(siCtrl)、MARCH5干涉组1(siMARCH5#1)与MARCH5干涉组2(siMARCH5#2),分别用葡萄糖摄取、乳酸生成、氧耗速率、ATP产生及代谢组学实验,分析下调MARCH5对卵巢癌细胞糖代谢的影响。结果与对照组SKOV3细胞相比,MARCH5干涉组1与干涉组2细胞的葡萄糖摄取[(1.00±0.06)vs(0.45±0.02)vs(0.44±0.02)]与乳酸产生[(1.00±0.05)vs(0.36±0.02)vs(0.35±0.03)]显著减少,而氧耗速率[(3.15±0.10)vs(5.73±0.14)vs(5.67±0.11)]与ATP含量[(1.00±0.04)vs(1.69±0.06)vs(1.74±0.07)]则显著升高,差异均有统计学意义(P<0.05);此外,与对照组SKOV3细胞相比,MARCH5干涉组1与干涉组2细胞内糖酵解代谢物显著减少,而线粒体三羧酸循环代谢物显著增多,差异均有统计学意义(P<0.05)。结论MARCH5促进了卵巢癌细胞糖代谢由氧化磷酸化向糖酵解的转变。

Objective To explore the role of membrane-associated RING-CH 5(MARCH5)in the regulation of glucose metabolism in ovarian cancer cells.Methods Glucose uptake,lactate production,oxygen consumption rate,ATP production,and cell metabolomics were analyzed in SKOV3 cells without(siCtrl group)or with(siMARCH5#1 group and siMARCH5#2 group)MARCH5 knockdown.Results Decreased glucose uptake[(1.00±0.06)in siCtrl group vs(0.45±0.02)in siMARCH5#1 group vs(0.44±0.02)in siMARCH5#2 group]and decreased lactate production[(1.00±0.05)vs(0.36±0.02)vs(0.35±0.03)],whereas increased oxygen consumption rate[(3.15±0.10)vs(5.73±0.14)vs(5.67±0.11)]and increased ATP production[(1.00±0.04)vs(1.69±0.06)vs(1.74±0.07)]were observed in SKOV3 cells when MARCH5 was knocked-down.Reduced metabolites in glycolysis and increased metabolites in TCA cycle were observed in SKOV3 cells when MARCH5 was knocked-down.Conclusion MARCH5 promotes glucose metabolism reprogramming in ovarian cancer cells through increasing glycolysis and decreasing oxidative phosphorylation.